Self-immolative linkers in polymeric delivery systems

There has been significant interest in the methodologies of controlled release for a diverse range of applications spanning drug delivery, biological and chemical sensors, and diagnostics. The advancement in novel substrate-polymer coupling moieties has led to the discovery of self-immolative linkers. This new class of linker has gained popularity in recent years in polymeric release technology as a result of stable bond formation between protecting and leaving groups, which becomes labile upon activation, leading to the rapid disassembly of the parent polymer. This ability has prompted numerous studies into the design and development of self-immolative linkers and the kinetics surrounding their disassembly. This review details the main concepts that underpin self-immolative linker technologies that feature in polymeric or dendritic conjugate systems and outlines the chemistries of amplified self-immolative elimination

Toxin-Antitoxin Pairs in Bacteria Killers or Stress Regulators?

AbstractPlasmid toxin-antitoxin systems, which kill daughter cells that fail to inherit the plasmid genome, have chromosomal homologs in eubacteria and archaea. In this issue of Cell, Pederson et al. show that the E. coli RelE toxin cleaves mRNA in the ribosomal A site, potentially allowing it to function as a stress regulator during amino acid starvation

Illuminating all-hadronic final states with a photon: Exotic decays of the Higgs boson to four bottom quarks in vector boson fusion plus gamma at hadron colliders

We investigate the potential to detect Higgs boson decays to four bottom quarks through a pair of pseudoscalars, a final state that is predicted by many theories beyond the Standard Model. For the first time, the signal sensitivity is evaluated for the final state using the vector boson fusion (VBF) production with and without an associated photon, for the Higgs at $m_H=125\,\textrm{GeV}$, at hadron colliders. The signal significance is $4$ to $6\sigma$, depending on the pseudoscalar mass $m_a$, when setting the the Higgs decay branching ratio to unity, using an integrated luminosity of $150\,\textrm{fb}^{-1}$ at $\sqrt{s}=13\,\textrm{TeV}$. This corresponds to an upper limit of $0.3$, on the Higgs branching ratio to four bottom quarks, with a non-observation of the decay. We also consider several variations of selection requirements - input variables for the VBF tagging and the kinematic variables for the photon - that could help guide the design of new triggers for the Run-3 period of the LHC and for the HL-LHC

Femoroacetabular Impingement as a Complication of Acetabular Fracture Fixation

Case We present the case of a thirteen-year-old female who sustained a posterior wall acetabular fracture dislocation. She underwent urgent closed reduction and subsequent uncomplicated open reduction and internal fixation. Post reduction computed tomography demonstrated a concentrically reduced hip joint with no evidence of femoroacetabular impingement (FAI). She subsequently healed her fracture and returned to running activities; however, one year later presented with aching pain in her thigh. Radiographs demonstrated the development of a large osseous prominence on her anterolateral femoral neck consistent with femoroacetabular impingement. Based on these findings she was evaluated by a hip preservation specialist. She subsequently underwent successful hip arthroscopy for labral repair and femoral osteochondroplasty. She was eventually able to return to running sports with little pain. Summary We present a case of FAI presenting as a complication of acetabular fracture fixation. This should be discussed with patients presenting with traumatic hip dislocations as a possible complication of surgical fixation or possibly of the injury itself

Insights Into the Deglacial Variability of Phytoplankton Community Structure in the Eastern Equatorial Pacific Ocean Using [\u3csup\u3e231\u3c/sup\u3ePa/\u3csup\u3e230\u3c/sup\u3eTh]xs and Opal-Carbonate Fluxes

Fully and accurately reconstructing changes in oceanic productivity and carbon export and their controls is critical to determining the efficiency of the biological pump and its role in the global carbon cycle through time, particularly in modern CO2 source regions like the eastern equatorial Pacific (EEP). Here we present new high-resolution records of sedimentary 230Th-normalized opal and nannofossil carbonate fluxes and [231Pa/230Th]xs ratios from site MV1014-02-17JC in the Panama Basin. We find that, across the last deglaciation, phytoplankton community structure is driven by changing patterns of nutrient (nitrate, iron, and silica) availability which, in turn, are caused by variability in the position of the Intertropical Convergence Zone (ITCZ) and associated changes in biogeochemical cycling and circulation in the Southern Ocean. Our multi-proxy work suggests greater scrutiny is required in the interpretation of common geochemical proxies of productivity and carbon export in the EEP

Integrated pest management in the academic small greenhouse setting: A case study using Solanum spp. (Solanaceae).

Premise Botanical faculty and staff at academic institutions are often tasked with establishing and/or caring for plant collections held in small greenhouse facilities. Once plants are in place, an especially acute challenge is managing plant pest/pathogen populations. Integrated pest management (IPM) approaches are an excellent option, but few examples exist in the literature of successful programs that have been developed in academic small greenhouse settings. Methods and Results Over several years, we developed an IPM program for two small research greenhouses on the campus of a primarily undergraduate institution where hundreds of plants have been grown for studies in the genus Solanum. We here present a synopsis of the cultural, mechanical, physical, and biological controls used as part of our successful IPM strategy—including details on the efficacy of multiple predatory insects—with the hope of providing a model for sustainable pest management in the higher education environment. Conclusions IPM can be an effective strategy for maintaining healthy plant populations in small research greenhouses, but it requires a consistent investment of time and funding. A well‐cared‐for plant collection might help support numerous positive outcomes, including advances in faculty scholarship and opportunities for student learning and/or training

Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

PurposeAcid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range.MethodsPublished reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis.ResultsDuration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis (p=0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis.ConclusionSignificantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children

A Foundational Population Genetics Investigation of the Sexual Systems of Solanum (Solanaceae) in the Australian Monsoon Tropics Suggests Dioecious Taxa May Benefit from Increased Genetic Admixture via Obligate Outcrossing

Solanum section Leptostemonum is an ideal lineage to test the theoretical framework regarding proposed evolutionary benefits of outcrossing sexual systems in comparison to cosexuality. Theoretically, non-cosexual taxa should support more genetic diversity within populations, experience less inbreeding, and have less genetic structure due to a restricted ability to self-fertilize. However, many confounding factors present challenges for a confident inference that inherent differences in sexual systems influence observed genetic patterns among populations. This study provides a foundational baseline of the population genetics of several species of different sexual systems with the aim of generating hypotheses of any factor—including sexual system—that influences genetic patterns. Importantly, results indicate that dioecious S. asymmetriphyllum maintains less genetic structure and greater admixture among populations than cosexual S. raphiotes at the same three locations where they co-occur. This suggests that when certain conditions are met, the evolution of dioecy may have proceeded as a means to avoid genetic consequences of self-compatibility and may support hypotheses of benefits gained through differential resource allocation partitioned across sexes. Arguably, the most significant finding of this study is that all taxa are strongly inbred, possibly reflective of a shared response to recent climate shifts, such as the increased frequency and intensity of the region’s fire regime

The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent manner

Most non-Hodgkin's lymphomas (NHL) initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma (MCL). Bortezomib exerts its activity in part through the generation of reactive oxygen species (ROS) and also by the induction of apoptosis